Activation of Serum Response Factor by RhoA Is Mediated by the Nuclear Factor-κB and C/EBP Transcription Factors

Transcriptional induction of the c-fos gene in response to epidermal growth factor stimulation is mediated in part by a ternary nucleoprotein complex within the promoter consisting of serum response factor (SRF), p62TCF/Elk-1 and the serum response element (SRE). Both SRF and p62TCF/Elk-1 contact the DNA and bind in a cooperative manner to the SRE. In this study, we demonstrate that SRF and Elk-1 interact directly in the absence of the SRE. A 30-amino-acid peptide from Elk-1 (B-box) is both necessary and sufficient to mediate protein-protein contacts with SRF. Moreover, the Elk-1 B-box is necessary to enable SRF-dependent binding of an alternative ETS domain (from the transcription factor PU.1) to the c-fos SRE. Mutations in either the Elk-1 B-box or the C-terminal half of the SRF DNA-binding domain (coreSRF) which show reduced ability to form ternary complexes also show greatly reduced protein-protein interactions in the absence of the SRE. Our results clearly demonstrate that direct protein-protein interactions between the transcription factors Elk-1 and SRF, in addition to DNA contacts, contribute to the formation of a ternary complex on the c-fos SRE. We discuss the wider applicability of our results in describing specific protein-protein interactions between short well-defined transcription factor domains.

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G-protein coupled receptor 56 promotes myoblast fusion through serum response factor- and nuclear factor of activated T-cell-mediated signalling but is not essential for muscle developmentin vivo

FEBS Journal ◽

10.1111/febs.12529 ◽

2013 ◽

Vol 280 (23) ◽

pp. 6097-6113 ◽

Cited By ~ 27

Author(s):

Melissa P. Wu ◽

Jamie R. Doyle ◽

Brenda Barry ◽

Ariane Beauvais ◽

Anete Rozkalne ◽

...

Keyword(s):

T Cell ◽

G Protein ◽

Serum Response Factor ◽

Myoblast Fusion ◽

Response Factor ◽

Nuclear Factor ◽

G Protein Coupled Receptor ◽

Activated T Cell ◽

G Protein Coupled ◽

Serum Response

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Interaction of Transcription Factors with Serum Response Factor

Journal of Biological Chemistry ◽

10.1074/jbc.273.17.10506 ◽

1998 ◽

Vol 273 (17) ◽

pp. 10506-10514 ◽

Cited By ~ 31

Author(s):

Yan Ling ◽

Adam G. West ◽

E. Claire Roberts ◽

Jeremy H. Lakey ◽

Andrew D. Sharrocks

Keyword(s):

Transcription Factors ◽

Serum Response Factor ◽

Response Factor ◽

Serum Response

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Nuclear Factor of Activated T Cells and Serum Response Factor Cooperatively Regulate the Activity of an α-Actin Intronic Enhancer

Journal of Biological Chemistry ◽

10.1074/jbc.m411972200 ◽

2005 ◽

Vol 280 (28) ◽

pp. 26113-26120 ◽

Cited By ~ 44

Author(s):

Laura V. Gonzalez Bosc ◽

Jeff J. Layne ◽

Mark T. Nelson ◽

David C. Hill-Eubanks

Keyword(s):

T Cells ◽

Serum Response Factor ◽

Response Factor ◽

Nuclear Factor ◽

Activated T Cells ◽

Intronic Enhancer ◽

Serum Response

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Calcium activates serum response factor-dependent transcription by a Ras- and Elk-1-independent mechanism that involves a Ca2+/calmodulin-dependent kinase.

Molecular and Cellular Biology ◽

10.1128/mcb.15.7.3672 ◽

1995 ◽

Vol 15 (7) ◽

pp. 3672-3684 ◽

Cited By ~ 156

Author(s):

C K Miranti ◽

D D Ginty ◽

G Huang ◽

T Chatila ◽

M E Greenberg

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Growth Factors ◽

Serum Response Factor ◽

Active Form ◽

Response Factor ◽

Transcriptional Responses ◽

Pheochromocytoma Cell ◽

Independent Mechanism ◽

Serum Response

Enhanced levels of cytoplasmic Ca2+ due to membrane depolarization with elevated levels of KCl or exposure to the Ca2+ ionophore ionomycin stimulate serum response element (SRE)-dependent transcription in the pheochromocytoma cell line PC12. By using altered binding specificity mutants of transcription factors that bind to the SRE, it was demonstrated that in contrast to treatment with purified growth factors, such as nerve growth factor, the serum response factor (SRF), but not Elk-1, mediates Ca(2+)-regulated SRE-dependent transcription. Enhanced levels of cytoplasmic Ca2+ were found to trigger SRE-dependent transcription via a Ras-independent signaling pathway that appears to involve a Ca2+/calmodulin-dependent kinase (CaMK). Overexpression of a constitutively active form of CaMKIV stimulated SRF-dependent transcription. Taken together, these findings indicate that SRF is a versatile transcription factor that, when bound to the SRE, can function by distinct mechanisms and can mediate transcriptional responses to both CaMK- and Ras-dependent signaling pathways.

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